The long-term objective of this Mentored Patient-Oriented Research Career Development (K23) Award is to develop the candidate's skills in applying functional imaging to patient-oriented clinical research so that he may become an independent investigator in the fields of dementia and neuroimaging. Dr. Greicius' specific research goal is to develop proficiency in the application of neuroimaging techniques to the early and accurate diagnosis of Alzheimer's disease (AD). To accomplish this goal, the candidate will be mentored by experts in the fields of functional imaging, aging and cognitive disorders, neuropsychology and statistics. In addition, the candidate will pursue an educational program to include advanced seminars in behavioral neurology and functional imaging as well as formal coursework in the areas of computer programming, neuropsychology and statistics. Finally, the candidate will undertake a research project closely aligned with his research training plan. The goal of the proposed research project is to develop a novel fMRI technique that will predict, with a high degree of certainty, which subjects at risk for AD will subsequently develop the disease. The study will use a novel fMRI approach, functional connectivity MRI (fcMRI), to examine three subject groups: A group with mild cognitive impairment (MCI), a group with mild-moderate AD, and a group of healthy older adults age- and gender-matched to subjects in the AD and MCI groups. The MCI group will be imaged at baseline and followed longitudinally with clinical and neuropsychological evaluations. The functional connectivity analysis will focus on a specific resting-state network (RSN) that incorporates several brain regions affected early in the course of AD including the posterior cingulate cortex (PCC), inferior parietal lobes, and hippocampus. The main hypotheses are that 1) functional connectivity analyses will demonstrate abnormal RSN activity in the AD group compared to age-matched controls and 2) abnormal activity in the RSN will reliably distinguish MCI patients who convert to AD from those MCI patients who do not. By conducting this research project and implementing the research training plan, Dr. Greicius plans to become an independent investigator in the fields of dementia and neuroimaging and contribute to the early detection and treatment of AD and other dementing diseases of the elderly.